Search results for: right sided colonic tumors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 495

Search results for: right sided colonic tumors

225 Mage Fusion Based Eye Tumor Detection

Authors: Ahmed Ashit

Abstract:

Image fusion is a significant and efficient image processing method used for detecting different types of tumors. This method has been used as an effective combination technique for obtaining high quality images that combine anatomy and physiology of an organ. It is the main key in the huge biomedical machines for diagnosing cancer such as PET-CT machine. This thesis aims to develop an image analysis system for the detection of the eye tumor. Different image processing methods are used to extract the tumor and then mark it on the original image. The images are first smoothed using median filtering. The background of the image is subtracted, to be then added to the original, results in a brighter area of interest or tumor area. The images are adjusted in order to increase the intensity of their pixels which lead to clearer and brighter images. once the images are enhanced, the edges of the images are detected using canny operators results in a segmented image comprises only of the pupil and the tumor for the abnormal images, and the pupil only for the normal images that have no tumor. The images of normal and abnormal images are collected from two sources: “Miles Research” and “Eye Cancer”. The computerized experimental results show that the developed image fusion based eye tumor detection system is capable of detecting the eye tumor and segment it to be superimposed on the original image.

Keywords: image fusion, eye tumor, canny operators, superimposed

Procedia PDF Downloads 337
224 Compartmental Model Approach for Dosimetric Calculations of ¹⁷⁷Lu-DOTATOC in Adenocarcinoma Breast Cancer Based on Animal Data

Authors: M. S. Mousavi-Daramoroudi, H. Yousefnia, S. Zolghadri, F. Abbasi-Davani

Abstract:

Dosimetry is an indispensable and precious factor in patient treatment planning; to minimize the absorbed dose in vital tissues. In this study, In accordance with the proper characteristics of DOTATOC and ¹⁷⁷Lu, after preparing ¹⁷⁷Lu-DOTATOC at the optimal conditions for the first time in Iran, radionuclidic and radiochemical purity of the solution was investigated using an HPGe spectrometer and ITLC method, respectively. The biodistribution of the compound was assayed for treatment of adenocarcinoma breast cancer in bearing BALB/c mice. The results have demonstrated that ¹⁷⁷Lu-DOTATOC is a profitable selection for therapy of the tumors. Because of the vital role of internal dosimetry before and during therapy, the effort to improve the accuracy and rapidity of dosimetric calculations is necessary. For this reason, a new method was accomplished to calculate the absorbed dose through mixing between compartmental model, animal dosimetry and extrapolated data from animal to human and using MIRD method. Despite utilization of compartmental model based on the experimental data, it seems this approach may increase the accuracy of dosimetric data, confidently.

Keywords: ¹⁷⁷Lu-DOTATOC, biodistribution modeling, compartmental model, internal dosimetry

Procedia PDF Downloads 199
223 External Vacuum Dressing: Optimising Non-Operative Management of Flail Sternum Post CPR

Authors: Nicholas Bayfield, Mark Newman

Abstract:

Case Presentation: A 48-year-old male was brought in by ambulance after an out-of-hospital cardiac arrest, with 20 minutes of good-quality cardiopulmonary resuscitation in the community. Return of spontaneous circulation was achieved with defibrillation, revealing an inferior ST-elevation myocardial infarction. He was revascularized emergently in the cath lab and stabilised. Following the procedure, he was noted to have paradoxical respiratory movements of the sternum and high oxygen requirements. CT imaging demonstrated a flail chest with bilateral anterior rib 1-7 fractures as well as a large left-sided extra-pleural haematoma and small haemopneumothorax, secondary to CPR. The patient’s ventilation was stabilised with oxygen via a high-flow humidifier. Pain relief was provided. The anatomy of his rib fractures was not easily amenable to operative fixation. In addition, he was considered to be a high-risk operative candidate due to his recent arrest. He was managed thus non-operatively with an external vacuum dressing applied to the anterior chest wall to minimise respiratory compromise and minimise pain from the motion around the rib fracture sites. Non-operative management was successful, and the patient was reviewed one month later. The paradoxical sternal movement had abated. Discussion: External vacuum dressing has been trialled for non-operative management of rib fractures with varying success. It provides an external brace to minimise fracture site movement during respiration and coughing, thus minimising pain. This modality should be considered a low-cost, high-reward adjunct to non-operative management of bony thoracic trauma.

Keywords: thoracic surgery, thoracic trauma, rib fractures, negative pressure dressing

Procedia PDF Downloads 134
222 Egg Yolk and Serum Cholesterol Reducing Effect of Garlic and Natural Cocoa Powder Using Laying Birds as Model

Authors: Onyimonyi Anselm Ego, Obi-Keguna Christy, Dim Emmanuel Chinonso, Ugwuanyi Evelyn, Uzochukwu Ifeanyi Emmanuel

Abstract:

A total of 144 Shaver Brown Layers in their sixteenth week of lay were used in a twelve weeks study to evaluate the egg yolk and serum cholesterol of the birds when fed varying dietary combinations of garlic and natural cocoa powder. The birds were randomly assigned into nine dietary treatments with 16 birds per treatment. Each bird was housed separately in a cage measuring 45 cm x 35 cm in an open sided battery cage house typical of the tropics. A standard poultry mash diet with 16.5% CP and 2800 KcalME/kg was formulated as the basal ration which also served as the control diet. Garlic and natural cocoa powder were incorporated in varying combinations (50 g or 100 g/100 kg of feed) in the remaining eight treatments. Weekly data of egg weight, egg length, egg diameter, yolk weight, albumen weight and hen day egg production were kept. Egg yolk and serum cholesterol levels were determined using a Randox kit. Results showed that birds receiving garlic and natural cocoa powder had significantly (P<0.05) reduced egg and albumen weight as compared to control birds. Hen day production of the birds was also significantly higher than control birds. Egg yolk and serum cholesterol of birds receiving the garlic and natural cocoa powder were significantly (P<0.05) lower than the control. Serum cholesterol levels showed decline in the birds receiving garlic and natural cocoa powder. The least yolk cholesterol level of 160 mg/dl was observed in birds receiving 50g garlic and 50 g natural cocoa powder (Treatment 5). Control birds had an egg cholesterol level of 245.45 mg/dl. It was concluded that incorporating garlic and natural cocoa powder in the diets of laying hens can result in a significant reduction in the egg and serum cholesterol levels.

Keywords: egg, serum, cholesterol, garlic

Procedia PDF Downloads 729
221 A Parallel Cellular Automaton Model of Tumor Growth for Multicore and GPU Programming

Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

Procedia PDF Downloads 216
220 Multiple Primary Pulmonary Meningiomas: A Case Report

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

Procedia PDF Downloads 92
219 An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

Procedia PDF Downloads 236
218 Disability Representation in Children’s Programs: A Critical Analysis of Nickelodeon’s Avatar

Authors: Jasmin Glock

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Media plays a significant role in terms of shaping and influencing people’s perception of various themes, including disability. Although recent examples indicate progressive attitudes in society, programs across genres continue to portray disability in a negative and stereotypical way. Such a one-sided or stereotypical portrayal of disabled people can further reinforce their marginalized position by turning them into the other. The common trope of the blind or visually impaired woman, for example, marks the character as particularly vulnerable. These stereotypes are easily absorbed and left unquestioned, especially by younger audiences. As a result, the presentation of disability as problematic or painful can instill a subconscious fear of disability in viewers at a very young age. Now the question arises, how can disability be portrayed to children in a more positive way? This paper focuses on the portrayal of physical disability in children’s programming. Using disabled characters from Nickelodeon’s Avatar: The Last Airbender and Avatar: The Legend of Korra, the paper will show that the chosen animated characters have the potential to challenge and subvert disability-based bias and to contribute to the normalization of disability on screen. Analyzing blind protagonist Toph Beifong, recurring support character and wheelchair user Teo, and villain Ming Hua who has prosthetic limbs, this paper aims at highlighting that these disabled characters are far more than mere stereotyped tokens. Instead, they are crucial to the outcome of the story. They are strong and confident while still being allowed to express their insecurities in certain situations. The paper also focuses on how these characters can make disability issues relatable to disabled and non-disabled young audiences alike and how they can thereby contribute to the reduction of prejudice. Finally, they will serve as an example of what inclusive, nuanced, and even empowering disability representation in animated television series can look like.

Keywords: Children, disability, representation, television

Procedia PDF Downloads 184
217 Protective Effect of Herniarin on Ionizing Radiation-Induced Impairments in Brain

Authors: Sophio Kalmakhelidze, Eka Shekiladze, Tamar Sanikidze, Mikheil Gogebashvili, Nazi Ivanishvili

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Radiation-induced various degrees of brain injury and cognitive impairment have been described after cranial radiotherapy of brain tumors. High doses of ionizing radiation have a severe impact on the central nervous system, resulting in morphological and behavioral impairments. Structures of the limbic system are especially sensitive to radiation exposure. Hence, compounds or drugs that can reduce radiation-induced impairments can be used as promising antioxidants or radioprotectors. In our study Mice whole-body irradiation with 137Cs was performed at a dose rate of 1,1 Gy/min for a total dose of 5 Gy with a “Gamma-capsule-2”. Irradiated mice were treated with Herniarin (20 mg/kg) for five days before irradiation and the same dose was administrated after one hour of irradiation. The immediate and delayed effects of ionizing radiation, as well as, protective effect of Herniarin was evaluated during early and late post-irradiation periods. The results reveal that ionizing radiation (5 Gy) alters the structure of the hippocampus in adult mice during the late post-irradiation period resulting in the decline of memory formation and learning process. Furthermore, Simple Coumarin-Herniarin reveals a radiosensitizing effect reducing morphological and behavioral alterations.

Keywords: ionizing radiation, cognitive impairments, hippocampus, limbic system, Herniarin

Procedia PDF Downloads 48
216 A Hybrid Feature Selection and Deep Learning Algorithm for Cancer Disease Classification

Authors: Niousha Bagheri Khulenjani, Mohammad Saniee Abadeh

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Learning from very big datasets is a significant problem for most present data mining and machine learning algorithms. MicroRNA (miRNA) is one of the important big genomic and non-coding datasets presenting the genome sequences. In this paper, a hybrid method for the classification of the miRNA data is proposed. Due to the variety of cancers and high number of genes, analyzing the miRNA dataset has been a challenging problem for researchers. The number of features corresponding to the number of samples is high and the data suffer from being imbalanced. The feature selection method has been used to select features having more ability to distinguish classes and eliminating obscures features. Afterward, a Convolutional Neural Network (CNN) classifier for classification of cancer types is utilized, which employs a Genetic Algorithm to highlight optimized hyper-parameters of CNN. In order to make the process of classification by CNN faster, Graphics Processing Unit (GPU) is recommended for calculating the mathematic equation in a parallel way. The proposed method is tested on a real-world dataset with 8,129 patients, 29 different types of tumors, and 1,046 miRNA biomarkers, taken from The Cancer Genome Atlas (TCGA) database.

Keywords: cancer classification, feature selection, deep learning, genetic algorithm

Procedia PDF Downloads 91
215 Rathke’s Cleft Cyst Presenting as Unilateral Visual Field Defect

Authors: Ritesh Verma, Manisha Rathi, Chand Singh Dhull, Sumit Sachdeva, Jitender Phogat

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A Rathke's cleft cyst is a benign growth found on the pituitary gland in the brain, specifically a fluid-filled cyst in the posterior portion of the anterior pituitary gland. It occurs when the Rathke's pouch does not develop properly and ranges in size from 2 to 40mm in diameter. A 38-year-old male presented to the outpatient department with loss of vision in the inferior quadrant of the left eye since 15 days. Visual acuity was 6/6 in the right eye and 6/9 in the left eye. Visual field analysis by HFA-24-2 revealed an inferior field defect extending to the supero-temporal quadrant in the left eye. MRI brain and orbit was advised to the patient and it revealed a well defined cystic pituitary adenoma indenting left optic nerve near optic chiasm consistent with the diagnosis of Rathke’s cleft cyst (RCC). The patient was referred to neurosurgery department for further management. Symptoms vary greatly between individuals having RCCs. RCCs can be non-functioning, functioning, or both. Besides headaches, neurocognitive deficits are almost always present but have a high rate of immediate reversal if the cyst is properly treated or drained.

Keywords: pituitary tumors, rathke’s cleft cyst, visual field defects, vision loss

Procedia PDF Downloads 179
214 Effects of Cell Phone Electromagnetic Radiation on the Brain System

Authors: A. Alao Olumuyiwa

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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.

Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)

Procedia PDF Downloads 320
213 Free Radical Dosimetry for Ultrasound in Terephthalic Acid Solutions Containing Gold Nanoparticles

Authors: Ahmad Shanei, Mohammad Mahdi Shanei

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When a liquid is irradiated with high intensities (> 1 W) and low frequencies (≤ 1 MHz) ultrasound, acoustic cavitation occurs. Acoustic cavitation generates free radicals from the breakdown of water and other molecules. The existence of particles in liquid provide nucleation sites for cavitation bubbles and lead to decrease the ultrasonic intensity threshold needed for cavitation onset. The study was designed to measure hydroxyl radicals in terephthalic acid solutions containing 30 nm gold nanoparticles in a near field of a 1 MHz sonotherapy probe. The effect of ultrasound irradiation parameters containing mode of sonication and ultrasound intensity in hydroxyl radicals production have been investigated by the spectrofluorometry method. Recorded fluorescence signal in terephthalic acid solution containing gold nanoparticles was higher than the terephthalic acid solution without gold nanoparticles. Also, the results showed that any increase in intensity of the sonication would be associated with an increase in the fluorescence intensity. Acoustic cavitation in the presence of gold nanoparticles has been introduced as a way for improving therapeutic effects on the tumors. Also, the terephthalic acid dosimetry is suitable for detecting and quantifying free hydroxyl radicals as a criterion of cavitation production over a range of condition in medical ultrasound fields.

Keywords: acoustic cavitation, gold nanoparticle, chemical dosimetry, terephthalic acid

Procedia PDF Downloads 449
212 Breast Cancer Diagnosing Based on Online Sequential Extreme Learning Machine Approach

Authors: Musatafa Abbas Abbood Albadr, Masri Ayob, Sabrina Tiun, Fahad Taha Al-Dhief, Mohammad Kamrul Hasan

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Breast Cancer (BC) is considered one of the most frequent reasons of cancer death in women between 40 to 55 ages. The BC is diagnosed by using digital images of the FNA (Fine Needle Aspirate) for both benign and malignant tumors of the breast mass. Therefore, this work proposes the Online Sequential Extreme Learning Machine (OSELM) algorithm for diagnosing BC by using the tumor features of the breast mass. The current work has used the Wisconsin Diagnosis Breast Cancer (WDBC) dataset, which contains 569 samples (i.e., 357 samples for benign class and 212 samples for malignant class). Further, numerous measurements of assessment were used in order to evaluate the proposed OSELM algorithm, such as specificity, precision, F-measure, accuracy, G-mean, MCC, and recall. According to the outcomes of the experiment, the highest performance of the proposed OSELM was accomplished with 97.66% accuracy, 98.39% recall, 95.31% precision, 97.25% specificity, 96.83% F-measure, 95.00% MCC, and 96.84% G-Mean. The proposed OSELM algorithm demonstrates promising results in diagnosing BC. Besides, the performance of the proposed OSELM algorithm was superior to all its comparatives with respect to the rate of classification.

Keywords: breast cancer, machine learning, online sequential extreme learning machine, artificial intelligence

Procedia PDF Downloads 93
211 Cyclic NGR Peptide Anchored Block Co-Polymeric Nanoparticles as Dual Targeting Drug Delivery System for Solid Tumor Therapy

Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

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Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

Procedia PDF Downloads 461
210 Chemopreventive Potency of Medicinal and Eatable Plant, Gromwell Seed on in Vitro and in Vivo Carcinogenesis Systems

Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki

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As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.

Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems

Procedia PDF Downloads 465
209 Intracranial Hypertension without CVST in Apla Syndrome: An Unique Association

Authors: Camelia Porey, Binaya Kumar Jaiswal

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BACKGROUND: Antiphospholipid antibody (APLA) syndrome is an autoimmune disorder predisposing to thrombotic complications affecting CNS either by arterial vasooclusion or venous thrombosis. Cerebral venous sinus thrombosis (CVST) secondarily causes raised intracranial pressure (ICP). However, intracranial hypertension without evidence of CVST is a rare entity. Here we present two cases of elevated ICP with absence of identifiable CVST. CASE SUMMARY: Case 1, 28-year female had a 2 months history of holocranial headache followed by bilateral painless vision loss reaching lack of light perception over 20 days. CSF opening pressure was elevated. Fundoscopy showed bilateral grade 4 papilledema. MRI revealed a partially empty sella with bilateral optic nerve tortuosity. Idiopathic intracranial hypertension (IIH) was diagnosed. With acetazolamide, there was complete resolution of the clinical and radiological abnormalities. 5 months later she presented with acute onset right-sided hemiparesis. MRI was suggestive of acute left MCA infarct.MR venogram was normal. APLA came positive with high titres of Anticardiolipin and Beta 2 glycoprotein both IgG and IgM. Case 2, 23-year female, presented with headache and diplopia of 2 months duration. CSF pressure was elevated and Grade 3 papilledema was seen. MRI showed bilateral optic nerve hyperintensities with nerve head protrusion with normal MRV. APLA profile showed elevated beta 2 glycoprotein IgG and IgA. CONCLUSION: This is an important non thrombotic complication of APLA syndrome and requires further large-scale study for insight into the pathogenesis and early recognition to avoid future complications.

Keywords: APLA syndrome, idiopathic intracranial hypertension, MR venogram, papilledema

Procedia PDF Downloads 151
208 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

Procedia PDF Downloads 53
207 SOCS3 Reverses Multidrug Resistance by Inhibiting MDR1 in Mammary Cell Carcinoma

Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

Procedia PDF Downloads 317
206 The Effect of Endurance Training and Taxol Consumption on Cyclooxygenase-2 and Prostaglandin E2 Levels in the Liver Tissue of Mice with Cervical Cancer

Authors: Alireza Barari, Maryam Firozi-Niyaki, Maryam Kamarlouei

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Background: Herbs have a strong anti-cancer effect. Also, exercise is one of several lifestyle factors known to lower the risk of developing cancer. The aim of this study was to investigate the effect of endurance training and taxol on cyclooxygenase-2 and prostaglandin E2 in the liver tissue of mice with cervical cancer. Materials and Methods: In this experimental study, 35 female C57 mice were randomly divided into 5 groups (n=7 in each group): control (healthy), control (cancer), complement (cancer), training-supplementary (cancer) and training (cancer). The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/kg/day of pure taxol was injected intra peritoneally. The dependent variables of this study were measured 24 hours after the last training session by ELISA. Results: The results showed that the use of taxol and endurance training reduced the levels of cyclooxygenase-2 and prostaglandin E2 in the liver tissues of C57 mice with cervical cancer. Conclusion: Induction of the cancerous tissue in mice with cervical cancer increases the levels of cyclooxygenase-2 and prostaglandin E2 and endurance training along with taxol may reduce these levels.

Keywords: cervical cancer, taxol, endurance training, cyclooxygenase-2, prostaglandin E2

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205 Brain Tumor Detection and Classification Using Pre-Trained Deep Learning Models

Authors: Aditya Karade, Sharada Falane, Dhananjay Deshmukh, Vijaykumar Mantri

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Brain tumors pose a significant challenge in healthcare due to their complex nature and impact on patient outcomes. The application of deep learning (DL) algorithms in medical imaging have shown promise in accurate and efficient brain tumour detection. This paper explores the performance of various pre-trained DL models ResNet50, Xception, InceptionV3, EfficientNetB0, DenseNet121, NASNetMobile, VGG19, VGG16, and MobileNet on a brain tumour dataset sourced from Figshare. The dataset consists of MRI scans categorizing different types of brain tumours, including meningioma, pituitary, glioma, and no tumour. The study involves a comprehensive evaluation of these models’ accuracy and effectiveness in classifying brain tumour images. Data preprocessing, augmentation, and finetuning techniques are employed to optimize model performance. Among the evaluated deep learning models for brain tumour detection, ResNet50 emerges as the top performer with an accuracy of 98.86%. Following closely is Xception, exhibiting a strong accuracy of 97.33%. These models showcase robust capabilities in accurately classifying brain tumour images. On the other end of the spectrum, VGG16 trails with the lowest accuracy at 89.02%.

Keywords: brain tumour, MRI image, detecting and classifying tumour, pre-trained models, transfer learning, image segmentation, data augmentation

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204 Differential Infection of Primary Human B-Cells and EBV Positive B-Lymphoma Cell Lines by Recombinant AAV Serotypes

Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

Abstract:

B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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203 The Differences of Vascular Endothelial Growth Factor Levels in Serum to Determine Follicular Adenoma and Follicular Carcinoma of Thyroid

Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto

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Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.

Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF

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202 Combined Analysis of m⁶A and m⁵C Modulators on the Prognosis of Hepatocellular Carcinoma

Authors: Hongmeng Su, Luyu Zhao, Yanyan Qian, Hong Fan

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Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that endanger human health seriously. RNA methylation, especially N6-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C), a crucial epigenetic transcriptional regulatory mechanism, plays an important role in tumorigenesis, progression and prognosis. This research aims to systematically evaluate the prognostic value of m⁶A and m⁵C modulators in HCC patients. Methods: Twenty-four modulators of m⁶A and m⁵C were candidates to analyze their expression level and their contribution to predict the prognosis of HCC. Consensus clustering analysis was applied to classify HCC patients. Cox and LASSO regression were used to construct the risk model. According to the risk score, HCC patients were divided into high-risk and low/medium-risk groups. The clinical pathology factors of HCC patients were analyzed by univariate and multivariate Cox regression analysis. Results: The HCC patients were classified into 2 clusters with significant differences in overall survival and clinical characteristics. Nine-gene risk model was constructed including METTL3, VIRMA, YTHDF1, YTHDF2, NOP2, NSUN4, NSUN5, DNMT3A and ALYREF. It was indicated that the risk score could serve as an independent prognostic factor for patients with HCC. Conclusion: This study constructed a Nine-gene risk model by modulators of m⁶A and m⁵C and investigated its effect on the clinical prognosis of HCC. This model may provide important consideration for the therapeutic strategy and prognosis evaluation analysis of patients with HCC.

Keywords: hepatocellular carcinoma, m⁶A, m⁵C, prognosis, RNA methylation

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201 Triplet Shear Tests on Retrofitted Brickwork Masonry Walls

Authors: Berna Istegun, Erkan Celebi

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The main objective of this experimental study is to assess the shear strength and the crack behavior of the triplets built of perforated brickwork masonry elements. In order to observe the influence of shear resistance and energy dissipating before and after retrofitting applications by using the reinforcing system, static-cyclic shear tests were employed in the structural mechanics laboratory of Sakarya University. The reinforcing system is composed of hybrid multiaxial seismic fabric consisting of alkali resistant glass and polypropylene fibers. The plaster as bonding material used in the specimen’s retrofitting consists of expanded glass granular. In order to acquire exact measuring data about the failure behavior of the two mortar joints under shear stressing, vertical load-controlled cylinder having force capacity of 50 kN and loading rate of 1.5 mm/min. with an internal inductive displacement transducers is carried out perpendicular to the triplet specimens. In this study, a total of six triplet specimens with textile reinforcement were prepared for these shear bond tests. The three of them were produced as single-sided reinforced triplets with seismic fabric, while the others were strengthened on both sides. In addition, three triplet specimens without retrofitting and plaster were also tested as reference samples. The obtained test results were given in the manner of force-displacement relationships, ductility coefficients and shear strength parameters comparatively. It is concluded that two-side seismic textile applications on masonry elements with relevant plaster have considerably increased the sheer force resistance and the ductility capacity.

Keywords: expanded glass granular, perforated brickwork, retrofitting, seismic fabric, triplet shear tests

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200 The Contribution of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Vascular Endothelial Growth Factor into the Unfavorable Clinical Course of Ulcerative Colitis

Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

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The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

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199 Craniopharyngiomas: Surgical Techniques: The Combined Interhemispheric Sub-Commissural Translaminaterminalis Approach to Tumors in and Around the Third Ventricle: Neurological and Functional Outcome

Authors: Pietro Mortini, Marco Losa

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Objective: Resection of large lesions growing into the third ventricle remains a demanding surgery, sometimes at risk of severe post-operative complications. Transcallosal and transcortical routes were considered as approaches of choice to access the third ventricle, however neurological consequences like memory loss have been reported. We report clinical results of the previously described combined interhemispheric sub-commissural translaminaterminalis approach (CISTA) for the resection of large lesions located in the third ventricle. Methods: Authors conducted a retrospective analysis on 10 patients, who were operated through the CISTA, for the resection of lesions growing into the third ventricle. Results: Total resection was achieved in all cases. Cognitive worsening occurred only in one case. No perioperative deaths were recorded and, at last follow-up, all patients were alive. One year after surgery 80% of patients had an excellent outcome with a KPS 100 and Glasgow Outcome score (GOS) Conclusion: The CISTA represents a safe and effective alternative to transcallosal and transcortical routes to resect lesions growing into the third ventricle. It allows for a multiangle trajectory to access the third ventricle with a wide working area free from critical neurovascular structures, without any section of the corpus callosum, the anterior commissure and the fornix.

Keywords: craniopharingioma, surgery, sub-commissural translaminaterminalis approach (CISTA),

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198 Prospects of Acellular Organ Scaffolds for Drug Discovery

Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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197 SOCS1 Inhibits MDR1 in Mammary Cell Carcinoma Reverses Multidrug Resistance

Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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196 Antiulcer Potential of Heme Oxygenase-1 Inducers

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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